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Targeting NOX, INOS and COX-2 in inflammatory cells: chemoprevention using food phytochemicals
Akira Murakami1, Hajime Ohigashi
1Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan. cancer@kais.kyoto-u.ac.jp
Abstract:
Biological, biochemical and physical stimuli activate inflammatory leukocytes, such as macrophages, resulting in induction and synthesis of proinflammatory proteins and enzymes, together with free radicals, as innate immune responses. On the other hand, chronic and dysregulated activation of some inducible enzymes, including NADPH oxidase (NOX), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, have been shown to play pivotal roles in the development of certain inflammatory diseases such as oncogenesis. While the use of synthetic agents, especially those targeting molecules, is an attractive and reasonable approach to prevent carcinogenesis, it should be noted that traditional herbs and spices also exist along with their active constituents, which have been demonstrated to disrupt inflammatory signal transduction pathways. In this mini-review, the molecular mechanisms of activation or induction of NOX, iNOS and COX-2, as well as some food phytochemicals with marked potential to regulate those key inflammatory molecules, are highlighted. For example, 1'-acetoxychavicol acetate, which occurs in the rhizomes of the subtropical Zingiberaceae plant, has been shown to attenuate NOX-derived superoxide generation in macrophages, as well as lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production through the suppression of iNOS and COX-2 synthesis, respectively. Notably, this phytochemical has exhibited a wide range of cancer prevention activities in several rodent models of inflammation-associated carcinogenesis. Herein, the cancer preventive potentials of several food phytochemicals targeting the induction of NOX, iNOS and COX-2 are described.
Insights
Certain food phytochemicals, like 1'-acetoxychavicol acetate from Zingiberaceae, can inhibit key inflammatory enzymes (NOX, iNOS, COX-2), potentially preventing inflammation-associated cancers.
Area of Science:
- Biochemistry
- Immunology
- Molecular Biology
Background:
- Inflammatory leukocytes, such as macrophages, produce proinflammatory molecules in response to stimuli.
- Chronic activation of enzymes like NADPH oxidase (NOX), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) is linked to inflammatory diseases, including cancer.
- While synthetic agents are used for cancer prevention, natural compounds from herbs and spices also show potential in disrupting inflammatory pathways.
Purpose of the Study:
- To review the molecular mechanisms underlying the activation of NOX, iNOS, and COX-2.
- To highlight food phytochemicals that can regulate these key inflammatory molecules.
- To discuss the cancer-preventive potential of these phytochemicals.
Main Methods:
- Review of literature on molecular mechanisms of NOX, iNOS, and COX-2.
- Identification and analysis of food phytochemicals targeting these enzymes.
- Examination of studies on cancer prevention activities of phytochemicals in animal models.
Main Results:
- 1 '-acetoxychavicol acetate, found in Zingiberaceae, reduces NOX-derived superoxide generation and suppresses iNOS and COX-2 synthesis.
- This phytochemical attenuates nitric oxide and prostaglandin E(2) production.
- 1 '-acetoxychavicol acetate demonstrates significant cancer prevention activities in rodent models of inflammation-associated carcinogenesis.
Conclusions:
- Food phytochemicals offer a promising avenue for regulating key inflammatory molecules involved in carcinogenesis.
- Targeting NOX, iNOS, and COX-2 with natural compounds like 1 '-acetoxychavicol acetate may be effective in cancer prevention strategies.
- Further research into phytochemicals can lead to novel approaches for managing inflammatory diseases and preventing cancer.
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